Bradykinin increases production of prostaglandin E-2 and prostacyclin as measured by radioimmunoassay. Both of these prostaglandins as well as PGE stimulate cAMP production and accumulation in cultured human foreskin fibroblasts. Responsiveness to bradykinin increases as cells approach confluency. Maintenance of confluent fibroblast without replacement of serum-containing medium is accompanied by a loss in responsiveness to bradykinin as measured by both cAMP accumulation and prostaglandin production. Incubation with fresh medium containing serum for at least 3 h restores responsiveness to bradykinin. The increment in cAMP produced by bradykinin is reduced when cells are incubated with isoproterenol, 8 Br-cAMP, phosphodiesterase inhibitors, and forskolin, agents which themselves increase cell cAMP content. These agents also inhibit the production of prostaglandins stimulated by bradykinin, suggesting that elevations in cAMP content may inhibit protaglandin production.